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In this study, electroporation-surface-enhanced Raman scattering (SERS) was applied to rapidly measure intracellular pH. The generation of a sensitive SERS probe for measuring pH in the range of 6.0-8.0 was accomplished through the conjugation of the pH-sensitive molecule 4-mercaptobenzoic acid (4-MBA) to the surface of gold nanoparticles (Au NPs) through its thiol functional group. This bioprobe was then rapidly introduced into nasopharyngeal carcinoma CNE-1 cells by electroporation, followed by SERS scanning and the fitting of intensity ratios of each detection point's Raman peaks at 1423 cm-1 and 1072 cm-1, to create the pH distribution map of CNE-1 cells. The electroporation-SERS assay introduces pH bioprobes into a living cell in a very short time and disperses the nanoprobe throughout the cytoplasm, ultimately enabling rapid and comprehensive pH analysis of the entire cell. Our work demonstrates the potential of electroporation-SERS for the biochemical analysis of live cells.

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The recurrence of nasopharyngeal carcinoma (NPC) is either at the local primary site or at regional or distant metastases. However, an axillary metastasis is a rare entity in NPC. We highlighted a case of recurrent NPC that presented with axillary swelling as the main initial complaint. Clinical examinations showed enlarged left axillary lymph nodes and left cervical lymph nodes. Histopathological examination of the axillary lymph node biopsy confirmed the recurrence of NPC. The patient underwent palliative chemotherapy in view of the advanced stage of recurrent disease. A thorough clinical history and examination during surveillance are crucial for early diagnosis and better survival outcomes.

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Head and neck cancers, including nasopharyngeal carcinoma (NPC), are relatively common in Saudi Arabia. Radiotherapy is a standard treatment for NPC, but it can lead to side effects, including post-radiation otitis media with effusion (OME). Managing post-radiotherapy OME remains a topic of debate, with various interventions proposed. This study aims to review the efficacy of different methods to manage post-radiotherapy OME in NPC. This includes tympanostomy tube insertion, frequent myringotomies, and observation. A systematic review was carried out for articles published between 1975 and 2023 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Excluded from the analysis were articles that involved patients undergoing surgical treatment for nasopharyngeal cancer, studies that focused on patients with other head and neck cancers who developed OME after radiotherapy, research investigating the effectiveness of surgical procedures unrelated to tympanostomy tube insertion, studies written in non-English language, and case reports, reviews, or conference letters. A total of 450 studies were screened, of which six studies were included in the review, yielding 328 patients. The mean age ranged between 46 and 52 years. Follow-up varied from six months to 11 years. The intervention in all studies was tympanostomy tube insertion, and the controls were myringotomy, observation, or tympanic membrane fenestration with cauterization. The use of recurrent myringotomies for the treatment of OME in patients with NP post-radiotherapy is associated with improved chances for the resolution of effusion and decreased risk of complications when compared to tympanostomy tube insertion. Hence, we recommend following a step-wise approach when dealing with this group of patients, offering grommets for patients with persistent effusion or those who cannot tolerate frequent procedures.

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Rhabdomyosarcoma (RMS) is a common soft tissue malignancy of the pediatric age group, frequently involving the head and neck region; however, nasopharyngeal RMS is a rare entity. By virtue of its parameningeal involvement and nonspecific presentations, nasopharyngeal RMS has become a clinical challenge to diagnose. We present a case of an eight-year-old boy presenting with signs and symptoms of nasal obstruction who was initially being treated for tonsillitis. Recurrent episodes led to detailed examination and radiologic imaging, and a diagnosis of Thornwaldt cyst was made. For the relief of symptoms, a debulking surgery was performed followed by a biopsy which revealed the mass to be a nasopharyngeal RMS. Our case highlights the importance of including nasopharyngeal RMS into the differentials of midline nasal masses along with the role of biopsy for confirming its diagnosis as treatment modalities for it are strikingly different than the other more common group of conditions, i.e., benign nasal masses. While surgery is usually delayed in the latter group, it can be of prime importance while treating nasal RMS, along with chemotherapy and radiotherapy.

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Photoimmunotherapy is a new treatment modality in which a tumor-targeting monoclonal antibody is combined with a photoactivated dye and a laser is applied to destroy tumor cells. In Japan, insurance reimbursement for this treatment started in January 2021 for unresectable locally advanced or locally recurrent head and neck cancer. We used photoimmunotherapy to treat two patients with recurrent nasopharyngeal squamous cell carcinoma (NPSCC). The first patient was diagnosed with NPSCC (T1N0M0) and treated with definitive radiotherapy, leading complete response. A local recurrence was observed and treated with photoimmunotherapy. Seven months have passed, complete response is archived. The second patient was diagnosed with NPSCC (cT2N1M1). Multimodal therapy led to a complete response for all lesions. A local recurrent lesion appeared, and photoimmunotherapy has been repeatedly performed. The lesion was controlled as a stable disease for about one year. Photoimmunotherapy could be an effective treatment for local recurrence of NPSCC after radiotherapy.

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BACKGROUND: Nasopharyngeal cancer (NPC) is a type of epithelial malignancy that is positive for Epstein-Barr virus (EBV) and affects several populations worldwide. Due to the high rates of relapse and metastasis following primary treatment, there is an urgent need to identify new candidates for NPC therapy. Recently, circular RNA (circRNA) has emerged as a promising target for cancer diagnosis and prevention. OBJECTIVE: This study aimed to study the circRNAs enriched in NPC patients, and further analyze potential signaling pathways involved. METHODS: A new bioinformatic tool named psirc was used to analyze RNA-sequencing datasets from NPC patients and normal specimens to study the NPC-enriched circRNAs. RESULTS: We identified and quantified the full-length circRNA in these samples and found the top 10 enriched circRNAs in NPC patients compared to control samples. Furthermore, we selected the most enriched circRNA, circEEF1A1_E8B1, and studied its protein coding ability, microRNA and RNA-binding protein (RBP) binding capacity. We also constructed a protein-protein interaction (PPI) network for its binding proteins and extracted hub genes. Finally, we conducted survival analysis for these hub genes in head and neck cancer patients. CONCLUSIONS: In summary, our study has revealed the presence of previously unidentified circRNAs that are enriched in NPC patients. Through an analysis of their molecular functions, we have advanced our understanding of the potential role of circRNAs in NPC development.

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PURPOSE: To determine the differences in supraclavicular lymph node metastasis between esophageal cancer (EC) and nasopharyngeal cancer (NPC) and explore the feasibility of differential supraclavicular clinical target volume (CTV) contouring between these two diseases based on the involvement of different fascial spaces. MATERIALS AND METHODS: One hundred patients with supraclavicular nodes positive for EC or NPC were enrolled, and their pre-treatment images were reviewed. The distribution patterns of nodes between the two diseases were compared in the context of node levels defined by the 2017 Japanese Esophageal Society and 2013 International Consensus on Cervical Lymph Node Level Classification. Grouping supraclavicular nodes based on sub-compartments formed by the cervical fascia was discussed, and the feasibility of differential CTV contouring based on the differences in the involvement of these sub-compartments between EC and NPC was explored. RESULTS: The 2013 Consensus on cervical node levels and 2017 Japanese Esophageal Society node station could not practically guide supraclavicular CTV contouring. We divided the supraclavicular space into six sub-compartments: the para-esophageal space (PES), carotid sheath space (CSS), sub-thyroid pre-trachea space (STPTS), pre-vascular space (PVS), and vascular lateral space (VLS) I and II. EC mainly spread to the PES, STPTS, CSS, and VLS I, whereas NPC tended to spread to the CSS, VLS I, and VLS II. These combinations of sub-compartments may help constitute the supraclavicular CTVs for EC and NPC. CONCLUSIONS: The fascia anatomy-based sub-compartments sufficiently distinguished metastasis to the supraclavicular space between EC and NPC, thus facilitating differential CTV contouring between these two diseases.

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Background Cancer is an ongoing global health concern; it is the greatest cause of mortality in the industrialized world and the second-highest cause of death in the developing world. This study aims to assess the incidence and geographic distribution of nasopharyngeal cancer between 2007 and 2016 in Saudi Arabia. Methods Data between 2007 and 2016 from Saudi Cancer Registry reports were collected in this study. These reports provide information on all cancer cases, including the age, sex, geographic location, and year of diagnosis for each patient. Result Between 2007 and 2016, the Saudi Cancer Registry identified 110,075 cancer cases in total. The mean age-standardized rate of all cancer types for women was 51.7 compared with 48.2 for men. The percentage of cases of nasopharyngeal cancers was 1.2% for women and 2.2% for men in 2007. This percentage decreased to 0.8% for women and increased to 2.7% for men in 2016 in comparison to all cancer cases. The curve for nasopharyngeal cancer of all cancer types for men and women correlated with rises and drops in men over the study period, and a minor decrease in women over time, until another rise in 2016. A positive correlation was observed between nasopharyngeal cancer incidence and age. The age-standardized rate data for nasopharyngeal cancer cases demonstrated a wide variation across Saudi regions. The age-standardized rate per 100,000 people from 2007 to 2016 ranged from 0.39 in Jazan to 1.92 in Qassim, with a national average of 1.06. Conclusion From 2007 to 2016, the overall trend of the age-standardized rate for men fluctuated while the female rate slightly dropped before rising again. On the contrary, the incidence of nasopharyngeal cancer varies by region in Saudi Arabia. Further study of this variation would help focus awareness campaigns on the most susceptible regions.

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Background: Platinum-containing doublet chemotherapy regimens are generally considered the standard first-line systemic therapy for recurrent or metastatic (R/M) nasopharyngeal cancer (NPC). Gemcitabine (GEM) plus cisplatin (CDDP) has become a standard therapy based on a phase 3 study in several countries, yet this regimen sometimes affects quality of life due to nausea or appetite loss. Here, we present the manageable toxicity and promising activity of paclitaxel + carboplatin + cetuximab (PCE) therapy for R/M NPC. Materials and Methods: We conducted a retrospective review of patients with R/M NPC who were treated with PCE from 2013 to 2019 at the National Cancer Center East, Kashiwa, Japan. PCE consisted of PTX 100 mg/m2 on days 1 and 8; CBDCA area under the blood concentration-time curve (AUC) 2.5 on days 1 and 8, repeated every 3 weeks; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly, as reported in the paper. Results: Fourteen patients were identified, consisting of 10 males and 4 females with a median age 59.6 years (range, 43-74). Among the 12 of 14 patients assessed for efficacy, overall response rate was 58.3%, with 2 complete responses and 5 partial responses. On median follow-up of 23.8 months, median overall survival was not reached with observed death events of 2. Median PFS was 4.1 months (95% CI, 2.6-5.6 months). Two patients experienced disease progression during cetuximab maintenance and restarted PCE treatment, then achieved partial response again. The most common grade 3 or 4 adverse events were neutropenia (21.4%) and skin reaction (14.3%). No treatment-related death was observed. Conclusion: Although the number of study population was small, our results suggest that PCE is feasible and potentially effective for R/M NPC, with a 58.3% response rate and 4.1-month PFS. Further prospective evaluation is warranted.

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Disulfiram/copper (DSF/Cu) is a promising antitumor reagent for clinical application due to its excellent anticancer activity and safety. However, the anticancer mechanism of DSF/Cu has not been fully elucidated. Our study showed that DSF/Cu strongly induced cytotoxic effects on both nasopharyngeal carcinoma (NPC) cells and α-smooth muscle actin (α-SMA)-positive fibroblasts. Fluorescence activated cell sorting (FACS) analysis further showed that DSF/Cu induced a higher late apoptosis rate in α-SMA-positive fibroblasts than in tumor cells, and DSF/Cu promoted apoptosis and necrosis by an aldehyde dehydrogenase (ALDH)-independent method. Furthermore, we found that the antitumor activity of DSF/Cu against NPC cells occurred through ROS/MAPK and p53-mediated ferroptosis pathways, and that the ROS scavenger N-acetyl-l-cysteine (NAC) could reverse the cellular and lipid ROS levels. In 5-8F xenografts, both TUNEL and immunohistochemical (IHC) analyses indicated that DSF/Cu could induce apoptosis and inactivate cancer-associated fibroblasts (CAFs) by inhibiting the expression of α-SMA. In addition, combined with cisplatin (CDDP), DSF/Cu was well tolerated in vivo and could significantly suppress the growth of NPC tissues. Our study demonstrated that DSF/Cu induced antitumor activity against both tumor cells, as well as CAFs and suggested that the use of DSF/Cu as an adjunctive therapy for NPC is worthy of consideration.

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Background: Vascular endothelial growth factor (VEGF) has been reported to serve as a promising prognostic marker in several cancers. This meta-analysis aims to assess the prognostic significance of VEGF in nasopharyngeal cancer (NPC). Methods: We conducted a systematic literature search of PubMed, Embase, and the Cochrane Library for observational studies published until June, 2018 to identify observational studies on the prognostic effect of tissue VEGF expression or serum VEGF level on the survival of NPC. The primary outcome measure assessed was overall survival (OS). The secondary outcomes included disease-free survival (DFS) or progression-free survival (PFS). Summary hazard ratio (HR) and its 95% confidence interval (95% CI) were derived using a random-effects model. Results: Out of 840 retrieved citations, 16 studies inclusive of 1,345 patients were included in the analysis of tissue VEGF expression and cancer survival. The pooled HRs for OS and DFS in patients with high VEGF expression were 2.07 (95% CI: 1.32-3.25) and 5.99 (95% CI: 2.66-13.48), respectively, with significant heterogeneity between studies (I2 = 79.1% for OS and 50.2% for DFS). Tissue high VEGF expression was not significantly associated with short RFS, PFS, or MFS. Five studies also investigated the prognostic effect between serum VEGF level and patient survival and found that high serum VEGF level was significantly associated with short OS for patients with NPC (HR 2.47, 95% CI 1.16-5.28), but not with short PFS (HR 1.47, 95% CI 0.92-2.35). Conclusions: Determination of tissue VEGF expression and serum VEGF level have the potential to serve as biomarkers and add prognostic information in NPC. Prospective analyses of associated data on VEGF expression and serum VEGF level in large NPC cohorts could be further conducted to advance our understanding of the relationship between VEGF and NPC outcomes.

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Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV) and characterized by peritumoral immune infiltrate. Advanced NPC has high lethality. Immunotherapy directed against EBV antigen targets has been previously explored in clinical trials, and is likely to be validated as an important target in NPC as randomized data emerges in the future. Cancer vaccines and adoptive T cell therapy have been explored in the clinic, with the latter showing the greatest success. Recent advances in gene sequencing technology now allow personalized tumor epitope mapping, whilst the advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis offers the opportunity to activate adaptive T cell response in vivo. Anti-PD1 antibodies have shown promising activity in early phase clinical trials, and randomized studies against chemotherapy are underway. As immunotherapy is incorporated into standard treatment paradigms, issues of optimal combinations with targeting agents, immune adjuvants, and sequence with chemotherapy and radiation therapy will need to be addressed. Effective strategies to increase tumor antigenicity, improve immunological memory and reduce immune escape, will need to be developed to improve treatment outcomes. Here we present a brief history of the evolution of immunotherapy in NPC, and highlight key concepts relevant to its further development in the clinic.

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Local or locoregional recurrence of nasopharyngeal carcinoma (NPC) after high-dose radiotherapy remains a significant clinical problem. This is especially important in regions of the world in which NPC is endemic, such as Southern China. In this review, we briefly present the evolution in the definitive treatment of NPC, but focus more so on the historical and contemporary treatment approaches and outcomes utilized in the recurrent setting. Specifically, we highlight the various treatment strategies (repeat surgery, brachytherapy, conventional re-irradiation, SRS/SBRT, and salvage IMRT), and their technical, physical and biological limitations. Special attention is given towards salvage IMRT, as this is becoming the standard of care for locally recurrent NPC. Further, it is the most commonly indicated modality, since it can be used to treat larger tumors and more extensive disease stages, which represent the majority of recurrent cases. Predictive and prognostic factors for the efficacy of repeat treatment are discussed as well. The toxicities brought about by repeat radiotherapy courses are also highlighted, with an emphasis on their impact on mortality and quality of life, which underscore the difficulty that this clinical entity presents. Lastly, the rationale for particle radiation therapy, which is potentially safer and more efficacious, for the treatment of locally recurrent NPC is presented.

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Since its establishment in 1957, the International Atomic Energy Agency (IAEA) has striven to promote global access to reliable and affordable radiotherapy, with much of its latest focus being in developing countries. While nasopharyngeal cancer (NPC) is highly curable by radiotherapy with excellent outcomes in developed countries, the outcomes in low- and middle-income countries (LMICs) are disappointing. Although the reasons for this are complex and multifactorial, improving the accessibility and quality of radiotherapy in these countries is fundamental. With concerted effort from experts and advocates around the world, ongoing initiatives are supported by the IAEA to combat the challenges in LMICs.

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Nasopharyngeal cancer (NPC) is a tumor of epithelial origin with complex etiology. Currently the standard treatment of NPC is radiotherapy, but therapy failure is quite common, making radioresistance an important issue. This study explores the association of specificity protein 1 (Sp1) protein expression with clinicopathological significance and disease prognosis in NPC patients receiving radiotherapy. A total of 82 NPC patients (55 males and 27 females, median age: 48 years old) were enrolled and received radiotherapy between September 2011 and March 2014. Tumor tissue and grossly adjacent normal mucosa were obtained in each patient. Sp1 expression was detected by western blot and immunohistochemical analysis, and the associations with clinicopathological status and radiotherapy response were analyzed. Our Results showed Sp1 protein expression was higher in CNE-1 and CNE-2 nasopharyngeal cancer cells than in normal nasopharyngeal mucosal NP69 cells. All 82 patients' tissue sections were stained positive for the Sp1 protein, and 39 (47.6%) patients showed higher level than adjacent normal mucosa. Sp1-overexpression in the tumor tissue was correlated with a higher tumor stage, nodal status, clinical stage and distant metastasis (P < 0.01). Patients with higher Sp1 expression in pretreatment biopsies had a lower radiotherapy response compared to those with lower expression. In conclusion, Sp1 may play roles in radioresistance of nasopharyngeal cancer which attributes to tumor invasiveness, and serve as a novel prognostic marker of NPC radiotherapy. However, further studies are required to validate our findings in larger samples and explore more detailed mechanisms underlying radioresistance of Sp1.

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This study aims to determine the optimal beam design among various combinations of field numbers and beam trajectories for intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) technique for the treatment of nasopharyngeal cancer (NPC). We used 10 fields with gantry angles of 155°, 130°, 75°, 25°, 0° L, 0° R, 335°, 285°, 230°, and 205° denoted as F10. To decrease doses in the spinal cord, the F10 technique was designed by featuring 2 pairs of split-opposed beam fields at 155° to 335° and 205° to 25°, as well as one pair of manually split beam fields at 0°. The F10 technique was compared with 4 other common field arrangements: F7E, 7 fields with 50° equally spaced gantry angles; F7, the basis of F10 with 155°, 130°, 75°, 0°, 285°, 230°, and 205°; F9E, 9 fields with 40° equally spaced gantry angles; and FP, 7 posterior fields with 180°, 150°, 120°, 90°, 270°, 240°, and 210°. For each individual case of 10 patients, the customized constraints derived after optimization with the standard F10 technique were applied to 4 other field arrangements. The 4 new optimized plans of each individual case were normalized to achieve the same coverage of planning target volume (PTV)63Gy as that of the standard F10 technique. The F10 field arrangement exhibited the best coverage in PTV70Gy and the least mean dose in the trachea-esophagus region. Furthermore, the F10 field arrangement demonstrated the highest level of conformity in the low-dose region and the least monitor unit. The F10 field arrangement performed more outstandingly than the other field arrangements in PTV70Gy coverage and spared the central organ. This arrangement also exhibited the highest conformity and delivery efficiency. The F10 technique is recommended as the standard beam geometry for the SIB-IMRT of NPC.

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